Receptores ativadores de proliferação perixossomal(PPARs) são fatores de transcrição envolvidos com a oxidação dos ácidos graxos e proliferação celular, mediando diversas vias, o que representa uma estratégia promissora para enfrentar as características da síndrome metabólica. Existem três isoformas de PPARs(PPARalfa, beta/delta e gama), que são diferencialmente expressos em diferentes tecidos.No presente estudo, objetivou-se avaliar os efeitos pleiotrópicos da telmisartana, um anti-hipertensivo, bloqueador do receptor AT1 da angiotensina e agonista parcial PPAR gama, no tecido adiposo branco (TAB) e marrom (TAM) em camundongos obesos induzido por dieta.Camundongos machos, da linhagem C57BL/6 foram alimentados com uma dieta padrão (standard-chow, 10% da energia proveniente de lipídios) ou com uma dieta com alto teor lipídico (high fat, 49% de energia proveniente de lipídios) durante 10 semanas. Em seguida, os animais foram distribuídos aleatoriamente em quatro grupos: SC, SC-T, HF e HF-T (n=10). O fármaco foi administrado (10mg/kg de dieta) durante 4 semanas para os grupos SC-T e HF-T.O grupo HF apresentou sobrepeso, hipertensão arterial sistêmica, perfil de adipocinas pró-inflamatórias, resistência insulínica, diminuição do gasto energético, comprometimento do metabolismo da glicose e distribuição anormal da massa adiposa. Além disso, a obesidade ocasionou diminuição da expressão de PPARalfa, beta/delta e gama noTAB e TAM, resultando na inadequação da captação de glicose e termogênese insuficiente. Por outro lado,a ativação das três isoformas de PPARs, a melhora do perfil inflamatório das adipocinas, o aumento da sensibilidade à insulina e a melhora da captação de glicose, foi vistaapós o tratamento com telmisartana. A ativação dos PPARs no TAB trouxe muitos benefícios. No TAM, resultados surpreendentes foram que a telmisartana provocou o aumento da expressão do recepetor adrenérgico beta 3 (RAβ3), induzido pela ativação de PPARbeta/delta e maior termogênese comaumento da expressão da proteína desacopladora1 (UCP1). Em conclusão, nossos resultados mostram que telmisartanaaumenta a expressão gênica e proteica PAN-PPAR no TAB e TAM em camundongos obesos induzidos por dieta. Nossas observações mostram que, apesar do grupo HF-T ter reduzido a ingestão energética, os efeitossão explicados pela ativação PAN-PPAR da telmisartana, causando a ativação da termogênese e resultando num balanço energético negativo. / Peroxisome proliferator-activated receptor (PPARs) are transcription factors involved in fatty acids oxidation and cell proliferation, mediating different pathways, representing a hopeful strategy to deal with the characteristics of metabolic syndrome. There are three isoforms of PPARs (PPAR alpha, beta / delta and gamma) that are differentially expressed in different tissues. The present study, aimed to evaluate pleiotropic effects of telmisartan, an anti-hypertensive, angiotensin receptor blocker AT1 and PPAR gamma agonist in white adipose tissue (WAT) and brown adipose tissue (BAT) in diet-induced obese mice. Male C57BL/6 mice fed a standard diet (standard-chow, 10% of energy from lipids) or a high fat diet (high fat, 49% of energy from lipids) for 10 weeks. Afterwards, groups were subdivided into: SC, SC-T, HF and HF-T (n=10, each). Treatment with telmisartan (10 mg/Kg BM, in the diet) was maintained for 4 weeks. The HF group showed overweight, hypertension, adipokine pro-inflammatory profile, insulin resistance, decreased in energy expenditure, flawed in glucose metabolism and abnormal distribution of adipose mass. Furthermore, obesity caused reduced expression of PPARalpha, beta/delta and gamma in WAT and BAT, resulting in unproductive glucose uptake and insufficient thermogenesis. On the other hand the activation of the three isoforms of PPARs, the improvement of the inflammatory profile, increased insulin sensitivity and improved glucose uptake was observed after treatment with telmisartan. The activation of PPARs in BAT provided many benefits. In BAT, surprising new findings show that telmisartan caused sympathetic activation with beta-3 adrenergic receptor (RAβ3), induced activation PPARbeta /delta and increased thermogenesis with increased expression of uncoupling protein 1 (UCP1), that it is a target gene of PPARalpha. In conclusion, our results show for the first time telmisartan increases the gene and protein expression PAN-PPAR in WAT and BAT in diet-induced obese mice. Our observations demonstrate that, although the HF-T group have reduced energy intake, the effects are explained by the PPAR-PAN activation of telmisartan, causing the activation of thermogenesis through maintaining sympathetic stimulation and increased expression of UCP1, resulting in a negative energy balance.

O ácido linoléico conjugado (CLA) é um ácido graxo poliinsaturado, encontrado nos produtos da alimentação. Estudos indicam que o CLA possui ações contra câncer, aterogênese e DM 2 e obesidade. O presente trabalho avaliou os efeitos da suplementação crônica com CLA em ratos Wistar machos e teve como objetivo investigar o desenvolvimento corporal e o perfil metabólico dos animais e dos adipócitos isolados do tecido adiposo branco periepididimal. Após quatro semanas de suplementação os animais apresentaram redução no ritmo de ganho de peso, acompanhado de redução da ingestão alimentar, redução da massa adiposa e do volume celular dos adipócitos. A menor incorporação dos substratos acetato e glicose em lipídeos, o aumento lipólise e diminuição da expressão do PPAR?, também contribuíram para menor adiposidade encontrada. A redução de massa adiposa foi acompanhada por resistência à insulina, elevados níveis de citocinas inflamatórias e desenvolvimento de esteatose hepática. Esses fatores estão relacionados com o desenvolvimento de síndrome lipodistrófica em animais. Portanto, a efetividade do CLA em reduzir massa adiposa foi comprovada no presente estudo, mas os efeitos devem ser considerados. / Conjugated linoleic acid (CLA) is a natural polyunsatured fatty acid found in many dietary sources. Animal studies demonstrated that CLA has properties against cancer, atherogenesis, diabetes and obesity. This work evaluated the effects with chronic CLA supplementation in young adults Wistar male rats for four weeks, aiming to investigate the possible changes in corporal development and metabolic profile as well as the effects in isolated adipocytes of periepidydimal white adipose tissue of these supplemented animals. We observed a reduction of the rhythym of body weight gain, followed by diminished food intake, regression of adipose mass, and also a reduction of adipocyte volume. The findings of low incorporation of acetate and glucose substrates into lipids, elevation on the lipolytic response and reduction of PPAR-gamma gene expression, also contributed to the lower adiposity. This reduction in adipose mass was followed by insulin resistance, high levels of inflammatory citokines and the development of hepatic steatosis, features related to the development of lipodystrophic syndrome. Therefore, this study demonstrated the CLA effect on reduction of adipose mass, although adverse effects associated with CLA chronic supplementation must be considered.

Fibroblast growth factor 21 (FGF21) is a unique peptide hormone involved in the energy homeosta- sis, as well as in the regulation of glucose and lipid metabolism. Numerous animal studies suggest that FGF21 may be used as a potential treatment for obesity and type 2 diabetes mellitus. It was found out, that FGF21 counteracts the development of obesity presumably by increasing energy expenditure through activation of thermogenesis in brown and white adipose tissue. FGF21 apparently also inhibits lipolysis. However, the specific mechanism of action of FGF21 is not clear. In our experiments we studied the antiobesogenic effects of FGF21 on mice model of diet-induced obesity at thermoneutrality. It is assumed that this model approach (in contrast to housing mice at standard laboratory temperature) mimics closely the metabolic status of humans. During the 4- to 8-day FGF21 treatment we observed a gradual reduction of lipid content in the brown and white adipose tissue and liver, especially in combination with β3-adrenergic stimulation. We have confirmed that FGF21 inhib- its lipolysis and also stimulates browning in certain adipose tissue depots. Furthermore, we have found that the effect of FGF21 on fatty acid secretion by adipose tissue is not mediated by changes in the fatty acid re-esterification...

Obesity is a serious problem in society today [1,2]. It might seems to have been caused simply by excess consumption of food compared to energy expenditure but obesity is actually a complex metabolic disorder centred on adipose lipid metabolism and cellular signalling systems linked to it [3]. Understanding the biology of adipose tissue (AT) is very important for the identification of novel and potential therapeutic targets in order to prevent and treat obesity-related disorders [4]. We utilized analytical approach liquid chromatography coupled to mass spectrometry (LC-MS) to study adipose tissue metabolism. Also, we were especially interested in the effect of omega-3 polyunsaturated fatty acids (PUFA) on that metabolism. Rodent and cell line experiments were performed and analyses were done of white adipose tissue (WAT), serum/plasma samples or cells as well as milk samples from mothers. At first, we established several ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods for analysis of acylcarnitines (AC), amino acids (AmA) and other metabolites. Importantly, these methods were able to distinguish isobaric species of AC which is not usually possible. Using these approaches we uncovered several acylcarnitines, i.e. long chain AC, carnitine, acylcarnitine C4 and...

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En dehors de son rôle dans la régulation de la balance hydrosodée, le récepteur minéralocorticoïde (MR) est un facteur de transcription hormono-dépendant qui exerce des effets pro-adipogéniques et anti-thermogéniques in vitro, mais son rôle dans la régulation du métabolisme énergétique in vivo n’a jamais été précisément étudié. Dans ce travail, nous avons montré que les souris surexprimant le MR humain (Tg) ont une résistance à l’obésité induite par le régime hyperlipidique. Ceci s’accompagne d’un défaut de développement de la masse adipeuse comme en témoignent des surfaces adipocytaires plus petites en histomoprhométrie et une diminution de l’expression de gènes impliqués dans l’adipogenèse tels que PPARγ2. Ce défaut d’adipogenèse n’est pas dû à une altération de la capacité intrinsèque des préadipocytes surexprimant le MR, isolés de la fraction stroma vasculaire, mais probablement à une modification de la polarisation macrophagique analysée par la technique du FACS. Ces résultats soulignent un impact immuno-métabolique de la surexpression du MR in vivo. Par ailleurs, dans notre modèle adipocytaire brun, nous démontrons que les corégulateurs du MR ont un profil d’expression différentiel pouvant rendre compte d’une coopération moléculaire au cours de la différenciation adipocytaire des cellules T37i. De plus, nous confirmons in vitro l’effet inhibiteur de l’aldostérone sur l’expression de UCP1 (Uncoupling protein 1). Enfin nous démontrons in vivo que la surexpression du MR dans le tissu adipeux brun des souris Tg induit une diminution de l’induction l’expression de UCP1 par une exposition au froid. L’ensemble de ces résultats apporte une meilleure compréhension du rôle du MR dans la régulation du métabolisme énergétique et devrait ouvrir des nouvelles perspectives thérapeutiques innovantes tels que l’utilisation de modulateurs sélectifs du MR dans le traitement des troubles métaboliques / Besides its role in the regulation of sodium homeostasis, the mineralocorticoid receptor (MR) is a hormone-dependent transcription factor that exerts pro-adipogenic and anti- thermogenic effects in vitro, but its role in vivo in the regulation of energy balance has never been precisely studied. In this study, we show that human MR overexpressing mice (Tg) were resistant to high fat diet-induced obesity. This was associated with a defect of fat mass as evidenced by smaller adipocyte size analyzed by histomorphometric study and a decreased expression of genes involved in adipogenesis such as PPARγ2. This alteration in adipogenesis was not related to a defect of the intrinsic capacity of MR overexpressing preadipocytes to differentiate into adipocytes, but probably to a change in macrophage polarization studied by FACS analysis. These results indicate an immuno-metabolic impact of MR overexpression in vivo. Moreover, in our brown adipocyte model, we demonstrate that MR coregulators have a differential expression profile, consistent with a coordinated and physiologically relevant cooperation occuring during brown adipogenesis. In addition, we confirm in vitro the inhibitory effect of aldosterone on UCP1 expression (Uncoupling protein 1). Finally, we demonstrate in vivo that MR overexpression in brown adipose tissue of Tg mice induced a decrease in the cold-induced UCP1 expression. Taken together, these results provide a better understanding of MR involvement in the regulation of energy metabolism and should open new therapeutic oportunities such as the use of selective MR modulators in the management of metabolic disorders.

Evidências na literatura demonstraram que o aumento da adiposidade confere maior suscetibilidade ao desenvolvimento de diabetes tipo 2, pois o tecido adiposo branco (TAB) atua na regulação da homeostasia energética e da sensibilidade à insulina através da sua atividade endócrina e de interações com reguladores neuroendócrinos. O treinamento físico aeróbio tem sido fortemente recomendado para a prevenção e tratamento do diabetes tipo 2, pois promove adaptações no metabolismo energético que contribuem diretamente para a melhora da resposta glicêmica e para o controle de peso corporal. Embora esteja claro na literatura o papel do treinamento físico contra o desenvolvimento de distúrbios no metabolismo da glicose e obesidade, uma lacuna de conhecimento ainda existe quando buscamos informações a respeito da participação metabólica do TAB na prevenção do diabetes tipo 2 através do treinamento físico aeróbio. Dessa forma, o presente estudo teve como objetivo testar a hipótese de que o efeito protetor do treinamento físico contra o desenvolvimento de diabetes tipo 2 é mediado por adaptações funcionais do TAB. Para isso, foram utilizados camundongos alimentados com dieta normocalórica e de cafeteria submetidos ou não ao treinamento físico aeróbio. O treinamento físico aeróbio foi eficaz para a prevenção do diabetes tipo 2, e essa resposta foi associada à menor adiposidade corporal resultante do aumento da lipólise e da capacidade oxidativa do TAB induzido pela maior ativação via da AMPK/ACC / Evidence in the literature have shown that increased adiposity confers greater susceptibility to developing type 2 diabetes and white adipose tissue (WAT) acts in the regulation of energy homeostasis and insulin sensibility through its endocrine activity and interaction with neuroendocrine regulators. Aerobic physical training has been strongly recommended for the prevention and treatment of type 2 diabetes because it promotes adaptations in the energy metabolism that contribute directly to the improvement of glycemic metabolism and body weight control. Although it is clear in the literature the role of physical training against the development of disturbances in the glucose metabolism and obesity, the role of WAT to prevent type 2 diabetes through physical training was poorly investigated. Thus, the present study aimed to test the hypothesis that the protective effect of physical training against the development of type 2 diabetes is mediated by functional adaptations of WAT. For this, we used mice fed with control or cafeteria diet and submitted or not to aerobic physical training. The physical training was effective for the prevention of type 2 diabetes, and this response was associated with lower body fat due to increased lipolysis and oxidative capacity of WAT induced by the activation of AMPK/ACC

Longtemps décrit comme un simple tissu de réserve énergétique, le tissu adipeux blanc est, depuis l’identification de la leptine en 1994, considéré comme un véritable organe endocrine. En effet, ce tissu secrète de nombreuses hormones et cytokines agissant de manière paracrine et endocrine pour contrôler le métabolisme énergétique. Par ailleurs, en plus des préadipocytes et des adipocytes, le tissu adipeux blanc contient également des cellules immunes innées et adaptatives ; lui conférant ainsi un rôle important dans le développement et le contrôle de l’immunité. Cependant, le rôle joué par le tissu adipeux blanc dans les infections - notamment pulmonaires - reste encore peu étudié. C’est dans ce cadre général que s’est inscrit ce travail de Thèse. La susceptibilité accrue des individus obèses (expansion du tissu adipeux blanc) à l’infection par le virus de la grippe (influenza) est largement étayée dans la littérature. Nous avons évalué l’impact de l’infection par le virus influenza sur le tissu adipeux blanc, chez des souris minces et des souris obèses. Nos résultats montrent que, de manière inattendue, le virus est détecté dans les tissus adipeux, sous-cutané (inguinal) et viscéral (périgonadique), de souris infectées par voie intra-nasale (détection du génome viral par RT-qPCR). La présence de virus dans le tissu adipeux est associée à l’augmentation de la sécrétion de cytokines pro- et anti-inflammatoires, à la diminution de l’expression de gènes impliqués dans la lipolyse et la lipogénèse, et à l’augmentation de l’expression des gènes impliqués dans l’induction d’une réponse immune anti-virale. De manière intéressante, l’infection par le virus influenza est associée au brunissement du tissu adipeux sous-cutané chez les souris minces. Chez les souris obèses, l’infection par le virus de la grippe n’induit pas l’effet dépôt spécifique observé chez la souris mince et ne montre pas de brûnissement au niveau du tissu adipeux sous-cutané 7 jours p.i. In vitro, nous montrons que le virus influenza peut infecter les préadipocytes et les adipocytes (lignée murine et cellules primaires humaines). Cependant, alors que le virus effectue la totalité de son cycle dans l’adipocyte, le préadipocyte libère très peu, voire pas, de nouveaux virions infectieux (PCR, transcriptomique, technique de plages de lyse, microscopie confocale et électronique). Ainsi nos résultats, très originaux, identifient le tissu adipeux blanc comme un nouveau tissu cible de l’infection par le virus de la grippe, in vivo. Au sein de ce tissu, les préadipocytes et les adipocytes sont potentiellement infectés par le virus, comme le montrent nos données in vitro, les adipocytes seuls permettant la production de nouvelles particules infectieuses.Contrairement à l’infection grippale, les données épidémiologiques et/ou expérimentales concernant la susceptibilité des obèses à l’infection par la bactérie Streptococcus pneumoniae sont contradictoires, du fait de l’utilisation de différents modèles d’obésité d’origine génétique et de sérotypes de pneumocoques. Dans ce projet, nous avons utilisé un modèle d’obésité d’origine nutritionnelle ; le modèle de souris nourries par un régime enrichi en lipides. Nous montrons que les souris obèses infectées (sérotype Sp1) développent un syndrome de type méningite, mortel, tandis que les souris minces contrôlent l’infection. Si les réponses pulmonaires à l’infection sont comparables entre les souris minces et obèses (dénombrement des colonies bactériennes, histologie, PCR, ELISA, cytométrie en flux), le nombre de bactéries dans le cerveau est significativement plus élevé chez les souris obèses, associé à une altération de la perméabilité de la barrière hématoencéphalique [...] / Since the identification of leptin in 1994, the white adipose tissue (WAT) is no longer considered to solely be an inert tissue storing fat. As an endocrine organ, the adipose tissue synthesizes and secretes several hormones and cytokines involved in the control of whole-body metabolism. In addition, besides preadipocytes and adipocytes, WAT also contains innate and adaptive immune cells; thereby contributing to the development and control of immunity. However, the role played by the adipose tissue during infections - notably during pulmonary infections, such as those resulting from influenza virus or Streptococcus pneumoniae infections - has barely been investigated. This defines the general scope of this work. Epidemiological and experimental data convincingly report that obese individuals are more susceptible to influenza infection. During this project, we therefore questioned whether influenza infection may impact on adipose tissues, both subcutaneous (inguinal, SCAT) and visceral (perigonadal, EWAT) depots, in lean and high-fat diet-induced obese mice. We unexpectedly showed that influenza virus is detected in SCAT and EWAT (quantification of the viral genome by RtqPCR) and that this was associated with drastic changes in the tissue such as: increased secretion of pro- and anti-inflammatory cytokines, decreased expression of genes involved in lipogenesis and lipolysis, as well as increased expression of genes related to the induction of anti-viral immunity. Interestingly enough, influenza infection was associated with the development of brown-like adipocytes in the SCAT, only in lean animals. Moreover, we demonstrated in vitro that preadipocytes and adipocytes (murine cell-line and human primary cells) are permissive to infection, yet with different outcomes. Indeed, only adipocytes allowed the release of new infectious particles (RtqPCR, transcriptomics, quantification of infectious particules on MDCK cells, confocal and transmission electron microscopy). Altogether, our findings revealed, for the first time, that the white adipose tissue, an organ at the crossroads of metabolism and immunity, is deeply affected by influenza infection and might thus be undervalued in influenza pathophysiology.In opposite to influenza infection, the impact of obesity on the outcome of Streptococcus pneumoniae (S.p.) infection remains uncertain, due to the different models (genetically-based obesity, and bacterial strains) used. During this work, we investigated S. pneumoniae (Sp1 strain, sublethal dose) infection in lean and high-fat diet-induced obese mice. We showed that obese mice died from sublethal S. pneumoniae infection, compared to lean animals. The increased mortality induced by infection did not result from impaired pulmonary response but rather from the development of a meningitis-like syndrom likely resulting from an increased bacterial dissemination through the bloodbrain barrier into the brain. We propose that the model of dietary obesity induced by consumption of fat-enriched diet, may be envisaged as a novel and valuable experimental model of memingitis to study Streptococcus pneumoniae travel through the blood-brain barrier and the subsequent immune consequences.

A diabetes mellitus (DM) é considerada uma das principais epidemias mundiais deste século, sendo responsável direta ou indiretamente pelo óbito de 123 mil diabéticos no Brasil em 2010. Na diabetes mellitus do tipo 1 (DM1), que corresponde a 5-10% dos casos, há ausência ou um relativo déficit de insulina circulante, acarretando aumento na glicemia e em produtos glicosilados, que por sua vez, podem estar relacionados à perda de visão e doenças cardiovasculares. Além disso, a marcante perda de tecido adiposo verificada na DM1 também pode acarretar hipercolesterolemia e esteatose hepática, além de possivelmente contribuir para a inflamação crônica característica da doença. Neste contexto, o objetivo principal do presente estudo foi examinar o efeito do treinamento de força e suplementação da dieta com leucina no tecido adiposo de ratos portadores de diabetes mellitus tipo 1. Para a realização do estudo, ratos Wistar machos foram aleatoriamente distribuídos em quatros grupos: i) Grupo DA (controle) (n=8) - sem treinamento (sedentário) e suplementado com uma mistura de aminoácidos não-essenciais (água ad libitum); ii) Grupo DL (n=8) - sem treinamento (sedentário) e suplementado com leucina (água ad libitum); iii) Grupo DTA (n=8) - com treinamento de força e suplementado com uma mistura de aminoácidos não-essenciais (água ad libitum); iv) Grupo DTL (n = 8) - com treinamento de força e suplementado com leucina (água ad libitum). Após 12 semanas de intervenção, os animais foram eutanasiados. Foram avaliados os seguintes parâmetros: lactato, tolerância à glicose, sensibilidade à insulina, consumo semanal de ração e água, evolução semanal do peso total dos animais, peso total do tecido adiposo e dos diferentes coxins; no soro: triacilglicerol (TAG), lipoproteína de alta densidade (HDL), colesterol total, TNF-α, IL-6, IL-10, IL-1β, leptina, adiponectina e insulina; no tecido adiposo retroperitoneal: expressão gênica de mTOR, Akt, 4E-BP, eif4E, p70s6k, PPARy, LPL, leptina, adiponectina e CEBP-α; concentração total de TNF-α, IL-6, IL-10, e IL-1β. A tolerância à glicose, o consumo de ração e água, a concentração total do TAB e do TARP, assim como a expressão gênica de mTOR, 4E-BP1, eif4E, p70S6k, PPARγ e CEBP-α encontraram-se melhorados nos grupos DL, DTA e DTL em comparação ao grupo DA; e as concentrações de HDL, colesterol total, IL-10 e adiponectina no soro, bem como a expressão gênica de adiponectina e a concentração total de IL-10 no TARP apresentaram-se aumentadas somente nos grupos DTA e DTL quando comparados ao grupo DA. Como conclusão, ambas intervenções foram capazes de atenuar as alterações fisiológicas verificadas na DM1, dentre eles as perdas excessivas do TAB. No entanto, por servir de estímulo para uma maior síntese de citocinas e hormônios antiinflamatórios por parte TAB, o treinamento de força foi o principal responsável pela redução da inflamação sistêmica dos animais. / Diabetes mellitus (DM) is considered one of the most important world epidemics of this century, being responsible directly or indirectly for the death of 123000 diabetics in Brazil in 2010. In type 1 diabetes (DM1), which corresponds to 5-10% of cases, there is absence or relative deficit of circulating insulin, leading to an increased glycemia and glycosilated products, which might be related to loss of vision and cardiovascular diseases. Furthermore, the marked loss of white adipose tissue (WAT) associated with DM1 might induce liver steatosis and hypercholesterolemia, besides possibly contributing to an increased chronic systemic inflammation. In this context, the main objective of the present study was examine the effect of resistance training and supplementation with leucine in the adipose tissue of type 1 diabetic rats. To conduct this study, Wistar male rats were randomly distributed in 4 groups: i) DA group (control of the experiment) (n=8) - without RT and supplemented with a mixture containing non-essential amino acids (water ad libitum); ii) DL group - without RT and supplemented with leucine (water ad libitum); iii) DTA group (n=8) - with RT and supplemented with a mixture containing non-essential amino acids (water ad libitum); iv) DTL group - with RT and supplemented with leucine (water ad libitum). After 12 weeks of intervention, animals were euthanized. The following parameters were analyzed: blood lactate, glucose tolerance, insulin sensitivity, weekly consumption of chow and water, evolution of total weight, WAT total weight and depots; concentration of triacylglycerol, high density lipoprotein, total cholesterol, TNF-α, IL-6, IL-10, IL-1β, adiponectin, leptin and insulin in the serum; gene expression of mTOR, 4E-BP1, eif4E, p70S6k, PPARγ, CEBP-α, LPL, leptin and adiponectin; in addition to the concentration of TNF-α, IL-6, IL-10, and IL- 1β in the retroperitoneal adipose tissue. Glucose tolerance, weekly consumption of chow and water, WAT and RPAT total weight, such as gene expression of mTOR, Akt, 4E-BP1, eif4E, p70S6k, PPARγ and CEBP-α were improved in DL, DTA and DTL groups in comparison with DA group; and the concentrations of HDL, total cholesterol, IL-10 and adiponectin in the serum, as well as gene expression of adiponectin and total concentration of IL-10 in the serum were increased only in DTA and DTL groups when compared to DA group. In conclusion, both interventions were capable of improving some DM1 physiological alterations, including the excessive loss of WAT. However, because resistance training stimulates an increased synthesis of antiinflammatory cytokines and hormones by WAT, this intervention might be the main responsible by the reduction of systemic inflammation of the animals.